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When the Women’s Health Initiative (WHI) trial of estrogen plus progestin was halted based on findings that the combination carried significant health risks that outweighed its benefits, women and healthcare providers around the country were left to navigate menopausal symptom management in a strange new world.

Hormone therapy (HT) quickly became a topic of great debate with some providers defending various regimens with others immediately pulling patients off any form of HT. Almost six years after the randomized trial was stopped, physicians and patients are still trying to decide the best way to strike a balance between safety and the effective management of severe menopausal symptoms.

Unfortunately, there may not be a single, simple answer. Instead, decisions about when and if to begin HT, how long to stay on the therapy or whether to look at other alternatives have become much more individualized.

Dr. Cynthia Stuenkel is a clinical professor of medicine in the Division of Endocrinology and Metabolism at the University of California-San Diego and a founding member of the North American Menopause Society (NAMS). As such, she has the opportunity to work with medical students, young physicians and peers who struggle with the decision to suggest HT for patients.

“The place I like to start,” she said, “is to give them permission to use hormone therapy for women with severe symptoms.”

She continued, “Many stopped using HT after the Women’s Health Initiative findings. I think that was reasonable given the information at the time. However, over the course of the last several years, there has been further analysis of the data from the WHI that I think provides a modicum of reassurance that for a healthy 50- to 59-year-old woman, their risk from hormone therapy is very low.”

She added that additional research is now being conducted, including looking at using lower doses of estrogen. Research is also considering the effect of introducing progestin at wider intervals, such as once every three to six months.

Bioidentical hormones are another area of great discussion.

“To my view, a bioidentical hormone is something a woman can swallow or absorb through her skin or vagina that has the same chemical structure as the hormones manufactured by her body,” said Stuenkel.

For patients who are interested in pursuing this form of HT, she noted, “The first thing I ask is ‘Does it work, and is it safe?’ The best way to figure that out is to look at large numbers of women in randomized trials.”

She added that several bioidentical options have indeed been evaluated and approved by the FDA. However, Stuenkel noted, the federal agency has recently initiated stronger actions against compounding pharmacies that do not include labeling regarding safety and content.

Sure to reignite discussion about HT, the March 5, 2008, issue of Journal of the American Medical Association featured results of the three-year WHI follow-up study of the 15,730 postmenopausal participants with an intact uterus who were part of the estrogen plus progestin trial. The study confirmed that some health risks from long-term use of combined HT therapy persist even several years after stopping the drugs.

Fortunately, the increased risks of cardiovascular events (heart attacks, blood clots and stroke) reported in women assigned to hormone therapy were no longer evident in the three years after stopping; protection from fractures and colon cancer, however, also disappeared once HT was stopped. A remarkable new finding was the increased risk of fatal and nonfatal cancers (mostly lung cancers) in women who had taken hormone therapy during the study (about 3 cases per 1000 women who used HT for a year). Providers are hopeful that more information is forthcoming to help put this new report in perspective.

Dr. Elizabeth Nabel, NHLBI director, said that the report “confirms the study’s primary conclusion that combination hormone therapy should not be used to prevent disease in healthy, postmenopausal women.”

The FDA recommends hormone therapy not be used to prevent heart disease. When HT is used for menopausal symptoms, the agency recommends it only be taken at the smallest dose and for the shortest time possible.

Dr. Stuenkel concurs that the FDA guidelines are key in evaluating patients for HT.

“The clear-cut indications as stated by the FDA and on the package are, number one, to remove vasomotor symptoms — hot flashes; number two, relieve vaginal symptoms of dryness and pain with intercourse; and the third indication is to protect their bones, and the FDA carefully says ‘for the prevention of osteoporosis.’”

Stuenkel said that while physicians should thoughtfully consider what is best for each patient, she thinks it is now possible to take a little more reassuring tone.

“While there are risks, they are small,” she said. “Most of us are using much lower doses than those used in the WHI and attempting to confine HT to younger women in their 50s.”

She continued, “I just hate to see women who are suffering not get help. I think we should not withhold therapy from women who need it.”

Perhaps the tone for 2008 is to find balance. Evidence renders the conclusion that HT should not be considered “automatic” for every woman of a certain age. For women with severe symptoms matching the FDA indications, however, a growing number of physicians say HT could be offered with a careful discussion of individual risks and benefits.



Novartis Now Offers Once-Yearly Osteoporosis Drug
For post-menopausal women, osteoporosis is a major threat to bone health. Now, Swiss drug manufacturer Novartis offers a once-a-year injection treatment to protect women.

Reclast® (zoledronic acid), which received FDA approval last summer, is administered in one 15-minute infusion session annually. It is part of the class of drugs known as bisphosphonates, which include the popular oral osteoporosis medications Fosamax®, Boniva® and Actonel®. The oral counterparts, however, must be taken daily, weekly or monthly.

In a company statement, Dr. Felicia Cosman of Columbia University pointed out that not all women are compliant with oral dosing. “For the first time we can ensure women receive a full year of the treatment they need to protect their bones.”

Results from a company-sponsored, randomized, double-blind trial showed significant three-year fracture risk reduction at key sites in comparison to placebo, including a 70 percent relative reduction in vertebral fracture, 41 percent reduction in hip fracture and 25 percent reduction in nonvertebral fracture (excluding finger, toe and craniofacial fractures). Furthermore, among the 7,700 women in the study, there was a significant increase in bone mineral density. Contraindications for receiving the injection include hypocalcemia and a hypersensitivity to zoledronic acid. Reclast contains the same active ingredient as Zometa® so the two shouldn’t be given in combination.



May 2008

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